Abstract Given the prevalence and morbidity of depression in later life, the inadequacies of current treatment approaches for averting years living with disability, the inequities in access to the mental health care delivery system, and the workforce shortages to meet the mental health needs of older Latinos, development and testing of innovative strategies to prevent depression and anxiety are of great public health significance and have the potential to change practice. In the proposed study, 240 older Latinos age 60+ with subthreshold depression or anxiety ? defined as ? 5 on the PHQ-9 OR GAD-7 ? will be randomized to either HOLA (n=120) or the healthy lifestyles education program (n=120). Participants will be followed for up to 24 months with repeated assessments of clinical, health-related, and psychosocial outcomes (at baseline, post intervention, 6, 12, 18, and 24 months post intervention). The study has three specific aims: (1a) to compare the effectiveness of HOLA and healthy lifestyles education in reducing risk factors for major depression and generalized anxiety disorder among older Latinos with subthreshold depression or anxiety; (1b) to compare the impact of HOLA and healthy lifestyles education in reducing the 2-year incidence and recurrence of major depression and generalized anxiety disorder among older Latinos with subthreshold depression or anxiety; (2) To compare the effectiveness of HOLA and healthy lifestyles education in improving health-related outcomes among older Latinos with minor or subthreshold depression or anxiety (e.g. pro and anti- inflammatory cytokines, objective measures of physical fitness, and health-related quality of life) among older Latinos with minor or subthreshold depression or anxiety; (3) and to identify biological and psychosocial sources of variability that are predictive of either therapeutic or adverse outcomes to treatment in older Latinos with subthreshold depression or anxiety. For Aims 1a and 2, the primary analytic strategy will be mixed effect modeling for main effects of group, time, and time-by-treatment interaction. For Aim 1b, the primary analytic strategy will be survival analysis of time to major depressive episode or generalized anxiety disorder in HOLA, healthy lifestyles education, and wait list control. For Aim 3, we will use a ?joint? model that integrates time-to-event models (i.e. Cox proportional hazards) with models for risk factor trajectories to explore the strongest predictors of treatment response or non-response, which is defined as a 50% decrease in symptom severity. Finally, we will determine whether preventive intervention effects, if detected, are mediated or moderated by changes in perceived social support or systemic inflammation. Health promotion interventions represent a potential solution to the multiple disparities experienced by older Latinos. Such an approach could appeal to older Latinos as a nonstigmatizing and culturally acceptable alternative to traditional mental health services.